This research is intended to identify events minimally necessary for tumor initiation or promotion, out of the numerous effects caused by single applications of initiators or promoters. The goal of the work proposed in this supplement application is to seek adducts of aromatic amines which may appear in smaller amounts from reactions with nucleic acids in vivo or in vitro than the known adduct 8-(N-2- fluorenylacetamido)guanine, but whose presence may offer a more unified explanation of the carcinogenicities of N-acetylarylamines. Adducts will first be prepared from sulfate esters of the compounds N-hydroxy-2- acetamidofluorene, N-hydroxy-2-acetamidophenanthrene, N-hydroxy-4- acetamidostilbene and N-hydroxy-4-acetamidobiphenyl with the nucleosides and deoxynucleosides of guanine, adenine and cytosine (the latter for acetamidostilbene only). The adducts obtained from the reactions of the acetate esters of the above-named N-hydroxy compounds with DNA and RNA in vitro will then be compared with the compounds obtained from reactions with the mononucleosides. Highly labeled acetate esters will then be applied to mice topically, the nucleic acids isolated from the epidermis, the time of maximum binding determined, and the identities of the adducts. Highly labeled N-arylacetamides will be injected into rats, the nucleic acids isolated from livers (of males and females) and mammary glands (females), the times of maximum binding determined, and the identities of the adducts. The findings obtained here are expected to have relevance to the concept of initiation of tumorigenesis by these compounds, and to form a basis for prediction of carcinogenicity or tumor-initiating potential from chemical principles.